NM_004791.3:c.148C>G

Variant names:

• chr13-101453932-C-G
• rs982820653
• NM_004791.3:c.148C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004791.3(ITGBL1):​c.148C>G​(p.Arg50Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000933 in 1,393,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.697
• Publications: 1 publications found

Genes affected

ITGBL1 (HGNC:6164): (integrin subunit beta like 1) This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18458953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.148C>G	p.Arg50Gly	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.148C>G	p.Arg50Gly	missense_variant	Exon 2 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-108+1001C>G		intron_variant	Intron 1 of 10		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.148C>G	p.Arg50Gly	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.148C>G	p.Arg50Gly	missense_variant	Exon 2 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-108+1001C>G		intron_variant	Intron 1 of 10	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000654 AC: 4 AN: 61204 AF XY: 0.0000571

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000671

GnomAD4 exome AF: 0.00000484 AC: 6 AN: 1240946 Hom.: 0 Cov.: 33 AF XY: 0.00000494 AC XY: 3 AN XY: 607762

African (AFR) AF: 0.00 AC: 0 AN: 25104

American (AMR) AF: 0.000168 AC: 3 AN: 17904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18838

East Asian (EAS) AF: 0.00 AC: 0 AN: 27740

South Asian (SAS) AF: 0.00 AC: 0 AN: 54412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41796

Middle Eastern (MID) AF: 0.000233 AC: 1 AN: 4298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1000688

Other (OTH) AF: 0.0000399 AC: 2 AN: 50166

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.000458 AC: 7 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000473 Hom.: 0

Bravo AF: 0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.148C>G (p.R50G) alteration is located in exon 2 (coding exon 2) of the ITGBL1 gene. This alteration results from a C to G substitution at nucleotide position 148, causing the arginine (R) at amino acid position 50 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.58	T;T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	.;L
PhyloP100		0.70
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.17
Sift	Benign	0.032	.;D
Sift4G	Benign	0.14	T;T
Polyphen		0.081	.;B
Vest4		0.41
MutPred		0.33		Gain of catalytic residue at G55 (P = 0.0048);Gain of catalytic residue at G55 (P = 0.0048);
MVP		0.41
MPC		0.76
ClinPred		0.18	T
GERP RS		0.42
Varity_R		0.30
gMVP		0.74
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs982820653; hg19: chr13-102106283;